NATURAL HISTORY OF SIVMAC BK28 & H824 INFECTION IN MACAQUES

在这个项目中，我们寻求识别疾病的早期预测因子 在M. nemestrina通过使用两个密切相关的 猴免疫缺陷病毒（SIV）攻击毒株， 在M.穆拉塔 使用 这些分子克隆提供了独特的机会， 并在使用分子定义的病毒时减缓艾滋病的进展。 进行病毒和免疫表征。 四只动物 感染SIVmacH 824（急性致病性）或BK 28 （最低致病性）。 感染SIVmacH 824的动物被 在感染后19和58周（PI）因AIDS样 症状 两只BK 28感染的动物在85周时被安乐死 PI;他们表现出CD 4下降，但尚未进展为AIDS。 对产精氨酸细胞的计数表明， Th 1型细胞因子对感染的反应，虽然没有 感染不同病毒的人之间 克隆 有趣的是，IFN_-产生细胞的峰值出现在 与病毒载量峰值同步。 胞内细胞因子 染色技术进行了改进，以允许分析的 抗原特异性细胞因子反应，这一进展将允许 更精确地测量对感染的免疫反应。 具有 开发了一种可靠的方法来测量RANTES的血浆水平，我们 结果表明，RANTES的表达在动物中被诱导并维持， 感染最小病原体（BK 28），而RANTES水平下降 在一只H824感染的动物中诱导后存活58 周 利用其他组织捐赠的样本进行的横断面研究 研究者支持这一发现，证明血浆RANTES 在感染高致病性 病毒 未来的项目将纳入从 这项研究旨在开发有效的治疗SIV和HIV诱导的 疾病 资助NIH拨款RR 00166。 Mulvania，T.，库恩，E.库勒， L.，Agy，M.B.，莫顿，W. R.，和Mullins，J.I. SIV的自然史 猕猴中mac BK 28和H824感染。 J. Med. Primatol. 27：87-93，1998.

In this project we seek to identify early predictors of disease progression in M. nemestrina through the use of two closely related simian immunodeficiency virus (SIV) challenge strains that differ markedly in their pathogenicity as determined in M. mulatta. The use of these molecular clones affords the unique opportunity to model fast and slow progression to AIDS while using molecularly defined viruses. Both viral and immune characterizations are performed. Four animals were infected with either SIVmacH824 (acutely pathogenic) or BK28 (minimally pathogenic). Animals infected with SIVmacH824 were euthanized at 19 and 58 weeks postinfection (PI) due to AIDS-like symptoms. The two BK28-infected animals were euthanized at 85 weeks PI; they demonstrated CD4 decline but had not yet progressed to AIDS. Enumeration of cytokine-producing cells demonstrated the induction of Th1-type cytokines in response to infection, although there were no significant differences between an imal s infected with different clones. Interestingly, peak numbers of IFN_-producing cells occurred synchronously with peak viral load. The intracellular cytokine staining technique was refined to allow for the analysis of the antigen-specific cytokine response, an advance that will allow for more precise measurement of the immune response to infection. Having developed a reliable method for measuring plasma levels of RANTES, we showed that RANTES expression was induced and maintained in animals infected with the minimal pathogen (BK28) while RANTES levels dropped after induction in the one H824-infected animal that survived 58 weeks. Cross-sectional studies utilizing samples donated by other investigators supported this finding, demonstrating that plasma RANTES levels are suppressed in animals infected with highly pathogenic viruses. Future projects will incorporate information obtained in this study to develop effective therapies for SIV- and HIV-induced disease. FUNDING NIH grant RR00166. Mulvania, T., Coon, E., Kuller, L., Agy, M.B., Morton, W.R., and Mullins, J.I. Natural history of SIV mac BK28 and H824 infection in Macaca nemestrina. J. Med. Primatol. 27:87-93, 1998.